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Publication Number
US-12274698-B2
Publication Date
2025-04-15
Expiration Date
Abstract
The present disclosure describes pharmaceutical formulations of bromocriptine and method of manufacturing and using such formulations. The formulations are useful for treating physiological disorders including improving glycemic control in the treatment of type 2 diabetes. Also disclosed is synthesis of bromocriptine citrate, and compositions and dosage forms containing bromocriptine citrate.
Core Innovation
The invention relates to bromocriptine formulation technology for treating metabolic disorders, including type 2 diabetes, obesity, prediabetes, and hyperlipidemia, by administering an effective amount of a pharmaceutical formulation comprising bromocriptine citrate and a triglyceride. The formulation is soluble in water to at least 200 mg/L at 20°C, and the document emphasizes improved aqueous solubility and improved heat, light, and water stability compared with traditional bromocriptine mesylate and bromocriptine mesylate/citrate formulations.
The formulations include bromocriptine citrate and triglyceride excipients that support aqueous solubility and stability in an aqueous environment. The description addresses water-facilitated degradation pathways and includes discussion of stability improvements connected with acidic excipients and triglyceride or lubricant-type components, including citric acid and triglyceride/fatty acid excipients such as stearic acid and hydrogenated castor oil.
The document further discloses formulation constraints associated with dissolution performance, impurity and related-substances control, and particle-size control. It specifies dissolution testing using a USP Apparatus Type 2 Paddle in 0.1 N hydrochloric acid and defines release behavior, while also describing impurity limits measured by HPLC with UV detection at 300 nm after defined storage conditions. Particle-size control is addressed through micronized bromocriptine with defined Dv90/Dv99/Dv10 thresholds.
Claims Coverage
The claims include one independent claim covering treatment of metabolic disorders using a water-soluble bromocriptine citrate/triglyceride formulation, and dependent claims that refine composition, dissolution, impurity control, and administration timing or dosage form. The main independent inventive feature is centered on water solubility of the formulation combined with bromocriptine citrate and a triglyceride for treating metabolic disorders selected from specific disease categories.
Water-soluble bromocriptine citrate with triglyceride for treating metabolic disorders
A method of treating a metabolic disorder selected from the group consisting of type 2 diabetes, obesity, prediabetes, and hyperlipidemia by administering an effective amount of a pharmaceutical formulation comprising bromocriptine citrate and a triglyceride, wherein the pharmaceutical formulation is soluble in water to at least 200 mg/L at 20°C.
Dissolution profile with at least about 80% release at about 30 minutes
The formulation has a dissolution profile where at least about 80% of bromocriptine citrate is released at about 30 minutes in USP Apparatus Type 2 Paddle Method at 50 rpm in 500 ml of 0.1 N hydrochloric acid at about 37°C.
Impurity control with no more than 3% total related substances after storage
The formulation contains no more than 3% total related substances as determined by HPLC with UV detection at 300 nm after storage at 40±2°C and about 70±5% relative humidity for about 6 weeks.
Minimum bromocriptine citrate dose of at least about 0.1 mg
The formulation provides a dose of at least about 0.1 mg of bromocriptine citrate.
Circadian-based administration timing tied to central nervous system dopamine activity
Administering the formulation at a time of day that increases central nervous system dopamine activity at the subject’s natural circadian peak, optionally administering so as to increase dopaminergic activity within 4 hours of waking.
Substantially free of magnesium and lactose
The formulation is substantially free of magnesium and lactose.
Overall claim coverage focuses on administering a water-soluble pharmaceutical formulation containing bromocriptine citrate and a triglyceride to subjects with metabolic disorders selected from type 2 diabetes, obesity, prediabetes, and hyperlipidemia. Dependent claim refinements include specific dissolution release behavior, impurity and related-substances limits under defined HPLC/UV testing and storage conditions, minimum bromocriptine citrate dose, substantially free of magnesium and lactose, and circadian-based dosing timing and specified dosage form.
Stated Advantages
Improved stability and solubility compared with traditional bromocriptine mesylate/citrate formulations.
Improved aqueous solubility compared with bromocriptine mesylate.
Enhanced heat and humidity stability.
Enhanced light stability.
Enhanced water stability in an aqueous environment.
Meets a dissolution performance criterion with at least about 80% bromocriptine citrate released at about 30 minutes under the specified dissolution conditions.
Limits impurities by having no more than 3% total related substances after storage under the specified conditions.
Documented Applications
Treating a metabolic disorder selected from the group consisting of type 2 diabetes, obesity, prediabetes, and hyperlipidemia in a subject by administering an effective amount of the bromocriptine citrate/triglyceride pharmaceutical formulation.
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